Folic acid supplementation in children with sickle cell disease: study protocol for a double-blind randomized cross-over trial
Abstract Background Sickle cell disease (SCD) is a genetic disorder which causes dysfunctional red blood cells (RBC) and is thought to increase requirements for folate, an essential B vitamin, due to increased RBC production and turnover in the disease. High-dose supplementation with 1–5 mg/d folic...
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| Format: | Article |
| Language: | English |
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BMC
2020-06-01
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| Series: | Trials |
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| Online Access: | http://link.springer.com/article/10.1186/s13063-020-04540-7 |
| _version_ | 1811339464153235456 |
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| author | Brock A. Williams Heather McCartney Erin Adams Angela M. Devlin Joel Singer Suzanne Vercauteren John K. Wu Crystal D. Karakochuk |
| author_facet | Brock A. Williams Heather McCartney Erin Adams Angela M. Devlin Joel Singer Suzanne Vercauteren John K. Wu Crystal D. Karakochuk |
| author_sort | Brock A. Williams |
| collection | DOAJ |
| description | Abstract Background Sickle cell disease (SCD) is a genetic disorder which causes dysfunctional red blood cells (RBC) and is thought to increase requirements for folate, an essential B vitamin, due to increased RBC production and turnover in the disease. High-dose supplementation with 1–5 mg/d folic acid, synthetic folate, has been the standard recommendation for children with SCD. There is concern about whether children with SCD need such high doses of folic acid, following mandatory folic acid fortification of enriched grains in Canada, and advancements in medical therapies which extend the average lifespan of RBCs. In animal and human studies, high folic acid intakes (1 mg/d) have been associated with accelerated growth of some cancers, and the biological effects of circulating unmetabolized folic acid (UMFA), which can occur with doses of folic acid ≥ 0.2 mg/d, are not fully understood. The objective of this study is to determine efficacy of, and alterations in folate metabolism from high-dose folic acid in children with SCD during periods of folic acid supplementation versus no supplementation. Methods In this double-blind randomized controlled cross-over trial, children with SCD (n = 36, aged 2–19 years) will be randomized to either receive 1 mg/d folic acid, the current standard of care, or a placebo for 12 weeks. After a 12-week washout period, treatments will be reversed. Total folate concentrations (serum and RBC), different folate forms (including UMFA), folate-related metabolites, and clinical outcomes will be measured at baseline and after treatment periods. The sum of the values measured in the two periods will be calculated for each subject and compared across the two sequence groups by means of a test for independent samples for the primary (RBC folate concentrations) and secondary (UMFA) outcomes. Dietary intake will be measured at the beginning of each study period. Discussion As the first rigorously designed clinical trial in children with SCD, this trial will inform and assess current clinical practice, with the ultimate goal of improving nutritional status of children with SCD. Trial registration ClinicalTrials.gov NCT04011345 . Registered on July 8, 2019 |
| first_indexed | 2024-04-13T18:27:01Z |
| format | Article |
| id | doaj.art-d7eaef5d080c4141baceba80b22f7e1a |
| institution | Directory Open Access Journal |
| issn | 1745-6215 |
| language | English |
| last_indexed | 2024-04-13T18:27:01Z |
| publishDate | 2020-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Trials |
| spelling | doaj.art-d7eaef5d080c4141baceba80b22f7e1a2022-12-22T02:35:14ZengBMCTrials1745-62152020-06-0121111110.1186/s13063-020-04540-7Folic acid supplementation in children with sickle cell disease: study protocol for a double-blind randomized cross-over trialBrock A. Williams0Heather McCartney1Erin Adams2Angela M. Devlin3Joel Singer4Suzanne Vercauteren5John K. Wu6Crystal D. Karakochuk7Food, Nutrition, and Health, Faculty of Land and Food Systems, The University of British ColumbiaDepartment of Pediatrics, Faculty of Medicine, The University of British ColumbiaDepartment of Pharmacy, BC Children’s HospitalBC Children’s Hospital Research InstituteSchool of Population and Public Health, The University of British ColumbiaBC Children’s Hospital Research InstituteBC Children’s Hospital Research InstituteFood, Nutrition, and Health, Faculty of Land and Food Systems, The University of British ColumbiaAbstract Background Sickle cell disease (SCD) is a genetic disorder which causes dysfunctional red blood cells (RBC) and is thought to increase requirements for folate, an essential B vitamin, due to increased RBC production and turnover in the disease. High-dose supplementation with 1–5 mg/d folic acid, synthetic folate, has been the standard recommendation for children with SCD. There is concern about whether children with SCD need such high doses of folic acid, following mandatory folic acid fortification of enriched grains in Canada, and advancements in medical therapies which extend the average lifespan of RBCs. In animal and human studies, high folic acid intakes (1 mg/d) have been associated with accelerated growth of some cancers, and the biological effects of circulating unmetabolized folic acid (UMFA), which can occur with doses of folic acid ≥ 0.2 mg/d, are not fully understood. The objective of this study is to determine efficacy of, and alterations in folate metabolism from high-dose folic acid in children with SCD during periods of folic acid supplementation versus no supplementation. Methods In this double-blind randomized controlled cross-over trial, children with SCD (n = 36, aged 2–19 years) will be randomized to either receive 1 mg/d folic acid, the current standard of care, or a placebo for 12 weeks. After a 12-week washout period, treatments will be reversed. Total folate concentrations (serum and RBC), different folate forms (including UMFA), folate-related metabolites, and clinical outcomes will be measured at baseline and after treatment periods. The sum of the values measured in the two periods will be calculated for each subject and compared across the two sequence groups by means of a test for independent samples for the primary (RBC folate concentrations) and secondary (UMFA) outcomes. Dietary intake will be measured at the beginning of each study period. Discussion As the first rigorously designed clinical trial in children with SCD, this trial will inform and assess current clinical practice, with the ultimate goal of improving nutritional status of children with SCD. Trial registration ClinicalTrials.gov NCT04011345 . Registered on July 8, 2019http://link.springer.com/article/10.1186/s13063-020-04540-7Sickle cell diseasePediatricsNutritionFolic acidMicronutrient supplementationRandomized control trial |
| spellingShingle | Brock A. Williams Heather McCartney Erin Adams Angela M. Devlin Joel Singer Suzanne Vercauteren John K. Wu Crystal D. Karakochuk Folic acid supplementation in children with sickle cell disease: study protocol for a double-blind randomized cross-over trial Trials Sickle cell disease Pediatrics Nutrition Folic acid Micronutrient supplementation Randomized control trial |
| title | Folic acid supplementation in children with sickle cell disease: study protocol for a double-blind randomized cross-over trial |
| title_full | Folic acid supplementation in children with sickle cell disease: study protocol for a double-blind randomized cross-over trial |
| title_fullStr | Folic acid supplementation in children with sickle cell disease: study protocol for a double-blind randomized cross-over trial |
| title_full_unstemmed | Folic acid supplementation in children with sickle cell disease: study protocol for a double-blind randomized cross-over trial |
| title_short | Folic acid supplementation in children with sickle cell disease: study protocol for a double-blind randomized cross-over trial |
| title_sort | folic acid supplementation in children with sickle cell disease study protocol for a double blind randomized cross over trial |
| topic | Sickle cell disease Pediatrics Nutrition Folic acid Micronutrient supplementation Randomized control trial |
| url | http://link.springer.com/article/10.1186/s13063-020-04540-7 |
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